HIV-1 resistance patterns to integrase inhibitors in Chilean patients with virological failure on raltegravir-containing regimens.

In this viewpoint we would like to describe our results in terms of resistance pattern in Chilean patients with virological failure (VF) on raltegravir (RAL)-containing-regimens and highlight the need for the concomitant availability of genotypic resistance testing to integrase strand transfer inhibitors (INSTIs) introduction in antiretroviral regimens, particularly in countries in South America. Indeed we found in our study the presence of two or more primary mutations in some of the participants which is associated with cross-resistance to all INSTIs. By using timely genotyping, we could optimally manage these patients, early after detection of VF.

Standardization of a colorimetric technique for determination of enzymatic activity of diamine oxidase (DAO) and its application in patients with clinical diagnosis of histamine intolerance.

BACKGROUND: Diamine Oxidase (DAO) has an essential role for degradation of exogenous histamine in the intestine; thus, histamine intolerance (HI) mainly has been correlated to a low concentration and/or activity of this enzyme. The objective of the study was to standardize a colorimetric technique to measure the enzymatic activity (function) of hDAO to then apply it to a series of 22 patients with a clinical diagnosis of HI. METHODS: For the standardization variables such as volume and type of sample, incubation time, wavelength of maximum absorption, types of substrates, and concentration of oxidized ascorbate were evaluated. Then the activity and concentration of DAO was determined in 22 patients diagnosed with HI and 22 healthy subjects. RESULTS: The mean of serum DAO concentration in the 22 patients was of 9.268 ± 1.124 U/mL. The mean of serum DAO concentration in the 22 controls was of 20.710 ± 2.509 U/mL, being significantly higher (P value 0.0002) the mean of the samples. The mean of serum DAO activity of the patients was of 1.143 ± 0.085 U/L and the controls was 1.533 ± 0.119 U/L, significantly greater than the patients (P value 0.011). In addition, the sensitivity of both techniques was 0.63. In the measuring of DAO concentration the specificity was 0.9, constituting a good diagnostic test, especially to rule out the true negatives. The determination of DAO activity had a specificity of 0.68. CONCLUSIONS: Although we used a small number of patients and controls and the absorbance values were lower than expected, statistically significant differences were found in the levels of concentration and DAO activity between the patients with histamine intolerance and the controls. Therefore, the measuring of DAO concentration and DAO activity is a good diagnostic strategy for study suspect cases of HI. The simultaneous use of both assays allows to reduce positive and negative false results, for example, patients with normal DAO levels that could present a dysfunction in the activity of this enzyme.

Efecto del raloxifeno en la función endotelial y la hemostasia en mujeres con enfermedad coronaria / Effects of raloxifene on endothelial function and hemostasis in women with ischemic heart disease

Introducción y objetivos. La modulación del tono vascular es uno de los efectos estrogénicos más relevantes. En mujeres posmenopáusicas, se ha propuesto un efecto beneficioso en la función endotelial del modulador selectivo del receptor estrogénico raloxifeno, aunque sus efectos en mujeres con cardiopatía isquémica establecida no han sido estudiados plenamente. Estudios recientes han generado controversia respecto al riesgo tromboembólico del raloxifeno. El objetivo del estudio es determinar el efecto del raloxifeno en: a) la función endotelial, y b) las vías de la coagulación y la fibrinolisis en mujeres posmenopáusicas con enfermedad coronaria. Métodos. El estudio MERCED es un ensayo prospectivo y aleatorizado que incluye a 33 mujeres posmenopáusicas con enfermedad coronaria. Se administra raloxifeno durante 3 meses, comparado con placebo, en un diseño cruzado y a doble ciego, y se analiza de forma seriada la función vascular y los parámetros biológicos relacionados con las vías de la coagulación. Resultados. Se ha observado una grave alteración de la vasodilatación mediada por flujo a nivel basal y el tratamiento con raloxifeno no ha modificado significativamente la función endotelial. El raloxifeno ha inducido un descenso de los valores de fibrinógeno (3,41 [3,11-3,74] frente a 3,69 [3,4-4]; p<0,05), los fragmentos F1+2 de la protrombina (0,93 [0,77-1,12] frente a 0,94 [0,78-1,15]; p<0,05) y los complejos plasmina/antiplasmina (211 [166-267] frente a 242 [199-295]; p<0,01). Conclusiones. El tratamiento a medio plazo con raloxifeno en mujeres con enfermedad coronaria no afecta a la función endotelial. Además, se ha documentado menor actividad trombótica y fibrinolítica con raloxifeno. Será necesario determinar si el riesgo trombótico adscrito al raloxifeno en estudios previos se asocia únicamente a subgrupos específicos de mujeres posmenopáusicas con enfermedad cardiovascular (AU)

Introduction and objectives. Modulation of vascular tone is one of the most relevant estrogen effects. A beneficial effect on endothelial function in postmenopausal women has also been proposed for the selective estrogen receptor modulator raloxifene. However, its effects in women with established cardiovascular disease have not been fully elucidated. In addition, recent trials have generated controversy regarding thromboembolic risk with raloxifene use. The aim of the study was to assess the effect of raloxifene on: a) endothelial function and b) coagulation and fibrinolysis pathways. Methods. The MERCED trial was a prospective, randomized clinical trial. Thirty-three postmenopausal women with ischemic heart disease were enrolled in the study. Raloxifene treatment was administered for a 3-month period, according to a double-blind crossover design. Assessment of vascular function and biologic parameters related to coagulation pathways were conducted at various pre-established time-points. Results. Flow-mediated dilatation was severely impaired in the study population, and raloxifene had no effect on endothelial function. Treatment with raloxifene was associated to decreased levels of fibrinogen (3.41 [3.11-3.74] vs. 3.69 [3.40-4.00], P<.05); prothrombin fragments F1+2 (0.93 [0.77-1.12] vs. 0.94 [0.78-1.15], P<.05); and plasmin/antiplasmin complexes (211 [166-267] vs. 242 [199-295], P<.01). Conclusions. The present study provides evidence that in postmenopausal women with demonstrated endothelial dysfunction and ischemic heart disease, mid-term treatment with raloxifene does not affect endothelial function. In the MERCED trial, no increased thrombotic risk was observed, but a decreased thrombotic and fibrinolytic activity was observed with raloxifene. Further studies are required to determine whether thrombotic risk is associated with specific clinical characteristics or subgroups of postmenopausal women with cardiovascular disease (AU)

[Effects of raloxifene on endothelial function and hemostasis in women with ischemic heart disease]. / Efecto del raloxifeno en la función endotelial y la hemostasia en mujeres con enfermedad coronaria.

INTRODUCTION AND OBJECTIVES: Modulation of vascular tone is one of the most relevant estrogen effects. A beneficial effect on endothelial function in postmenopausal women has also been proposed for the selective estrogen receptor modulator raloxifene. However, its effects in women with established cardiovascular disease have not been fully elucidated. In addition, recent trials have generated controversy regarding thromboembolic risk with raloxifene use. The aim of the study was to assess the effect of raloxifene on: a) endothelial function and b) coagulation and fibrinolysis pathways. METHODS: The MERCED trial was a prospective, randomized clinical trial. Thirty-three postmenopausal women with ischemic heart disease were enrolled in the study. Raloxifene treatment was administered for a 3-month period, according to a double-blind crossover design. Assessment of vascular function and biologic parameters related to coagulation pathways were conducted at various pre-established time-points. RESULTS: Flow-mediated dilatation was severely impaired in the study population, and raloxifene had no effect on endothelial function. Treatment with raloxifene was associated to decreased levels of fibrinogen (3.41 [3.11-3.74] vs. 3.69 [3.40-4.00], P<.05); prothrombin fragments F(1+2) (0.93 [0.77-1.12] vs. 0.94 [0.78-1.15], P<.05); and plasmin/antiplasmin complexes (211 [166-267] vs. 242 [199-295], P<.01). CONCLUSIONS: The present study provides evidence that in postmenopausal women with demonstrated endothelial dysfunction and ischemic heart disease, mid-term treatment with raloxifene does not affect endothelial function. In the MERCED trial, no increased thrombotic risk was observed, but a decreased thrombotic and fibrinolytic activity was observed with raloxifene. Further studies are required to determine whether thrombotic risk is associated with specific clinical characteristics or subgroups of postmenopausal women with cardiovascular disease. Full English text available from: www.revespcardiol.org.

Posicionamiento de la Asociación Española para el Estudio de la Menopausia sobre el uso clínico de la Cimicífuga racemosa en el climaterio / Position statement of the Spanish Menopause Society on the Clinical Use of Cimicifuga racemosa during menopause

Objetivo: Dado el creciente interés en los países occidentales acerca de la utilización de ciertas plantas para el tratamiento de los síntomas relacionados con la menopausia, la AsociaciónEspañola para el Estudio de la Menopausia (AEEM)ha evaluado el papel de la Cimicífuga racemosa en el tratamiento de los síntomas climatéricos sobre la base de las mejores evidencias disponibles. Material y métodos. Se reunió un panel de expertos, clínicos e investigadores, en el campo dela fitoterapia. Los estudios seleccionados se obtuvieron mediante una búsqueda electrónica que incluyó buscadores de Internet, MEDLINE (1985-mayo 2008) y el Registro de Ensayos Clínicos Controlados Cochrane. Resultados: La mayoría de los estudios publicados en los últimos años están realizados con el extractoisopropanólico de Cimicífuga racemosa. La dosis más estudiada ha sido 40 mg/día y ha demostrado obtener una reducción moderada de las sofocaciones, sobre todo en las mujeres con sofocos más intensos, y una mejoría del estado de ánimo. Utilizada a las dosis recomendadas, no hay riesgo relevante desde el punto de vista hepático. Los datos disponibles sobre su efecto en la enfermedad cardiovascular, el hueso, la función cognitiva y la piel son muy escasos o inexistentes. Conclusiones: La Cimic ífuga racemosa es un tratamiento eficaz en el alivio de los síntomas vasomotores, al menos en una población adecuada de mujeres peri y posmenopáusicas, si bien se precisan mejores ensayos clínicos con suficiente número de pacientes incluidas y mayor duración del estudio (AU)

Objective: Due to an increasing interest in the symptoms related to menopause in western countries, the Spanish Menopause Society (SMS)has assessed the role of cimicifuga racemosa in relieving those symptoms based on the mostreliable evidence available. Material and methods: A meeting was held with a panel of experts, health scientists and researchers specialised in the field of phytotherapy. The studies selected were obtained through electronic search which included INTERNET, MEDLINE (1985-May 2008), and the Cochrane Controlled Clinical Trials Register. Results: Most studies published in recent years have been carried out using an isopropanol extract of cimicifuga racemosa. The dose most commonly studied was 40mg/day and was shown to result ina moderate decrease in hot flushes, particularly in those women with the most intense hot flushes, and an improvement in their mood. When recommended doses are used there is no significant risk to the hepatic system. Available data on the effect of cimicifuga racemosa on cardiovascular disease, bones, cognitive function or skin are scarce or non-existent. Conclusions: Cimicifuga racemosa is an effective treatment for relief of vasomotor symptoms, at least within a suitable population of peri- and postmenopausal women. Nevertheless, more accurate clinical trials which include sufficient numbers of patients and a longer follow-up are required (AU)

Posicionamiento de la Asociación Española para el Estudio de la Menopausia sobre el uso clínico de las isoflavonas en el climaterio / The use of isoflavones during climaterium: position statement of the Spanish Menopause Society

Objetivo: Existe un interés creciente en los países occidentales acerca de la utilidad de las isoflavonas de la soja para el tratamiento de los síntomas y enfermedades relacionadas con la menopausia y el envejecimiento, que se ha traducido en la aparición de un importante número de publicaciones, muchas de las cuales presentan resultados contradictorios. La Asociación Española para el Estudio de la Menopausia (AEEM) ha evaluado el papel de las isoflavonas en la salud de la mujer menopáusica, basándose en las mejores evidencias disponibles. Material y métodos: Se reunió un panel de expertos, clínicos e investigadores en el campo de las isoflavonas. Los estudios seleccionados se obtuvieron mediante una búsqueda electrónica que incluyó buscadores de internet, Medline (1966-marzo de 2007) y el Registro de Ensayos Clínicos Controlados Cochrane. Resultados: Las diferentes revisiones y metaanálisis sobre los efectos de las isoflavonas en la salud de la mujer son controvertidos. La diversidad de resultados puede deberse, entre otras causas, a la falta de uniformidad de los compuestos estudiados. En relación con la dosis y el contenido en genisteína, se han demostrado efectos beneficiosos en el perfil lipídico, como antioxidantes, así como una reducción moderada de los sofocos. Algunos estudios sugieren un efecto positivo en la masa ósea. Los datos disponibles en otros aspectos, como la mama, cánceres dependientes de los estrógenos, función cognitiva y piel, entre otros, son escasos. Conclusiones: En diversas situaciones, las isoflavonas pueden ser una alternativa terapéutica en el climaterio, si bien antes de poder proceder a la realización de recomendaciones generales acerca del consumo de preparados de isoflavonas, se necesitan ensayos clínicos específicos, de diseño adecuado, con preparados normalizados en cuanto al contenido en isoflavonas y sus tipos, y con suficiente número de pacientes y tiempo de estudio

Introduction: Western countries have shown an increasing interest in the use of soya isoflavones to treat aging and menopause-related diseases and their associated symptoms, stimulating a proliferation of studies, many of which report contradictory results. Consequently, the role of isoflavones was assessed by the Spanish Menopause Society (SMS) using the most reliable scientific evidence. Material and methods: A panel of experts on isoflavones was gathered. The selected studies were obtained by electronic search engines, Medline (1966-March 2007) and the Cochrane Controlled Clinical Trials Registry. Results: The various reviews and meta-analysis on the effects of Isoflavones on women's health are controversial. The contradictory results may be due, among other factors, to the lack of uniformity in the compounds under study. Data on doses and genisteine content have indicated beneficial effects on lipid profile, like antioxidants, as well as a mild decrease in hot flushes. Some studies suggest a positive effect on bone mass. However few data are available on other aspects such as breast, estrogen-dependent cancer, cognitive function, or skin Conclusions: In certain situations, isoflavones can be a therapeutic alternative during the climacteric period. However, before general recommendations on the use of isoflavone supplements can be made, more specific clinical trials should be performed. These studies should be adequately designed, with supplements that are standarized according to isoflavone content and types, a sufficient number of patients and study duration

Effect of surgical menopause and Paget's disease of bone on the isomerization of type I collagen carboxyterminal telopeptide: evolution after antiresorptive therapy.

The objective of this study was to analyze the effect of surgical menopause and Paget's disease of bone, as well as the influence of therapy, on the isomerization of the carboxyterminal telopeptide of type I collagen (CTX). Fourteen women who had undergone surgical menopause and had begun hormone replacement therapy (HRT) after surgery were recruited. Results for these women were compared with those of 29 patients with Paget's disease of bone treated with tiludronate (400 mg/day) for 3 months, and with those of a group of 21 healthy premenopausal women (control group I). In addition, 14 healthy individuals with an age range similar to that of the pagetic patients (control group II) were included in the study. Urine samples were analyzed for levels of nonisomerized and beta-isomerized CTX (alpha-CTX and beta-CTX). Biochemical determinations were performed 3 months after surgical menopause and after 3 and 9 months of HRT, and at baseline, and 1 and 6 months after tiludronate treatment in the pagetic patients. The average levels of alpha-CTX and beta-CTX were higher in patients than in controls. In patients after surgical menopause, because of their greater increase of beta-CTX, the alpha-CTX/beta-CTX ratio was lower than that of control group I (0.881 +/- 0.3 vs 1.515 +/- 0.8; P < 0.05). In contrast, at baseline, pagetic patients showed marked increases in alpha-CTX levels, resulting in a higher alpha-CTX/beta-CTX ratio than that of control group II (2.879 +/- 1.3 vs 0.96 +/- 0.25; P < 0.0001). The average percent decrease in both markers after therapy was similar in both conditions (-60% for alpha-CTX and -44% for beta-CTX after 3 months of HRT in the surgical menopause group, vs -66% for alpha-CTX and -41% for beta-CTX in the pagetic group, 1 month after finishing tiludronate therapy; P, NS), resulting in a significant decrease of the alpha-CTX/beta-CTX ratio in pagetic patients (2.879 +/- 1.3 vs. 1.614 +/- 0.8; P < 0.001). In conclusion, surgical menopause is associated with a decrease in the urinary alpha-CTX/beta-CTX ratio because of the higher increase in the beta-CTX level after menopause. Pagetic patients show an increase in this ratio, compared with the control value, and the ratio decreases after bisphosphonate treatment. The response to therapy was similar in both conditions, with a comparable decrease of both markers. These findings show how bone markers may contribute to the understanding of pathophysiologic mechanisms in bone diseases.